To assess the efficacy and safety of recombinant human follicle-stimulating hormone (rhFSH; follitropin alpha) in increasing sperm concentration in 26 men with severe isolated hypogonadotropic hypogonadism (IHH).
Clinical and endocrine studies using an open design.
Six university clinical sites in three European countries.
Azoospermatic patients aged 16 to 48 years with IHH.
Patients received hCG for up to 6 months before 18 months of treatment with rhFSH. Sperm count, motility, and morphology were assessed every 3 months.
Achievement of a sperm concentration of 1.5 x 10(6)/mL.
Spermatogenesis was achieved in 15 of 19 patients who could be evaluated, 12 achieving a sperm concentration of > or =1.5 x 10(6)/mL.
With hCG, rhFSH is effective in initiating spermatogenesis in patients with IHH, and is well tolerated.
"In males with hypogonadotrophic hypogonadism presented by azospermia or sever oligoasthenoteratospermia, rFSH may be effective in achieving spermatogenesis when combined with HCG.141–144 Combined analysis of data from four clinical trials shows that HCG and rFSH induced spermatogenesis in 84% of men with hypogonadotrophic hypogonadism.145 A number of baseline factors, including mean testicular volume, body mass index, age of disease onset and response to previous therapy, has been shown to influence the response.145,146 "
[Show abstract][Hide abstract] ABSTRACT: Recombinant human follicle stimulating hormone (rFSH) and luteinizing hormone (LH), also known as follitropin alpha and lutropin alpha, are manufactured by genetic engineering techniques which ensure high quality and batch to batch consistency. Follitropin alpha can be used for controlled ovarian hyperstimulation in assisted reproduction, ovulation induction for WHO group I and II anovulatory infertility and in men with hypogonadotrophic hypogonadism (HH) or idiopathic oligo-asthenospermia. Current evidence suggests superiority of urinary human menopausal gonadotropin (HMG) over follitropin alpha in controlled ovarian hyperstimulation for IVF in terms of live birth rate per couple. Addition of lutropin to follitropin alpha in an unselected IVF population does not appear to confer any benefit; however, it may have a role in ovulation induction in women with hypothalamic hypogonadism. Urinary HMG preparations (especially currently available highly purified preparations) are more cost effective than rFSH in terms of cost per ongoing pregnancy. However, women using rFSH injection pen devices have higher levels of satisfaction as compared to those using urinary HMG by means of conventional syringes.
"Combined administration of hCG and rFSH activated spermatogenesis in the majority of patients. The dose of rFSH used by us (150 IU/week) in association with hCG was lower than that used by others in previous studies which employed 450 IU a week to restore spermatogenesis in hypogonadal men (Liu et al., 1999; Bouloux et al., 2002). "
[Show abstract][Hide abstract] ABSTRACT: In adult men, anti-Müllerian hormone (AMH) levels are higher in semen than in serum, but the significance and control of its seminal secretion are still unknown. This study evaluated seminal and serum AMH levels during long-term gonadotropin therapy in men with hypogonadotropic hypogonadism (HH).
A total of 20 men with never treated prepubertal-onset HH received i.m. hCG to normalize testosterone (T) and induce puberty. Afterwards, 11 of them, requiring fertility, were treated with HCG plus recombinant FSH (rFSH) (75 IU) twice a week, whereas 9 continued to receive hCG alone for 12 months. Before and during therapy, serum AMH, inhibin B and T levels were assessed. Semen samples were also collected during therapy for sperm count and seminal AMH assay.
HCG alone decreased basal high serum AMH and stimulated T and inhibin B levels. rFSH plus hCG increased seminal AMH levels, which were consequently significantly higher than with hCG alone, and positively correlated to sperm densities and testicular volumes at 3 and 12 months (P < 0.001).
Our data demonstrate that rFSH, added to hCG, stimulates seminal AMH and spermatogenesis in HH. Thus, seminal AMH levels are under T and FSH control and are closely related to progression of spermatogenesis. Our results also suggest that an early seminal AMH increase may be a marker of good future response to gonadotropin therapy in HH.
Human Reproduction 05/2008; 23(5):1029-34. DOI:10.1093/humrep/den046 · 4.57 Impact Factor
"Schill et al.  reported no decrease in serum T levels in patients with azoospermia after an average of 18 months following non-microsurgical TESE. However, the same study indicated that patients with NOA had lower serum T levels and that T response to human chorionic gonadotrophin (HCG) stimulation were more frequently impaired compared to men with obstructive azoospermia . Therefore, they concluded that patients with NOA show an increased risk of androgen deficiency following non-microsurgical TESE and recommended long-term follow-up in this group of patients . "
[Show abstract][Hide abstract] ABSTRACT: The aim of our study was to review the results of microsurgically performed testicular sperm extraction (TESE) and to evaluate its possible long term effects on serum testosterone (T).
We operated on 48 men (35 +/- 8 years) with non-obstructive azoospermia (NOA). If no spermatozoa were found following a micro epididymal sperm extraction (Silber et al., 1994) and testicular biopsy, testicular microdissection was performed or multiple microsurgical testicular biopsies were taken. The mean follow-up of the serum T was 2.4 +/- 1.1 years.
Sperm was retrieved in 17/48 (35%) of the men. The per couple take home baby rate if sperm was retrieved was 4/17 (24%). Serum T decreased significantly at follow-up (p < 0.05) and 5/31 (16%) de novo androgen deficiencies developed
In patients with non-obstructive azoospermia in whom no spermatozoa were found following a micro epididymal sperm aspiration and a simple testicular biopsy, we were able to retrieve spermatozoa in 35% of the men. The take home baby rate was 24% among couples with spermatozoa present upon TESE. De novo androgen deficiency occurred in 16% of the male patients following TESE indicating that, in men with NOA, long term hormonal follow up is recommended after TESE.
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